Upper respiratory mucosal congestion caused by infections such as the common cold and influenza, or allergic rhinitis, can lead to a number of nasal and ocular symptoms. These include rhinitis and sinusitis, nasal and sinus congestion or excessive secretions, headaches, sneezing and itching and excessive lacrimation. Infections such as the common cold can be very common over the winter months, while the symptoms of rhinitis are also common in some parts of the world.
Such symptoms can be treated with antihistamine containing products and with decongestant containing products. The products are generally sold as part of non-prescribed medicines which are available to patients through outlets such as pharmacies.
There are a number of antihistamine actives available including non-sedating antihistamines such as loratadine, cetirizine or fexofenadine. These products provide less sedation in comparison to normal antihistamines, and therefore more readily allow a user to perform tasks such as driving or operating machinery.
Fexofenadine is an active carboxylic acid metabolite of terfenadine. The latter has been withdrawn due to serious cardiotoxic reactions and drug interactions. In depth information regarding the risk of these reactions is not available for fexofenadine. But according to the AHFS Drug Information 2004 as a result of comparative studies between fexofenadine and terfenadine, it is thought that the clinical efficacy of terfenadine is attributable to fexofenadine.
The risk of similar reactions to terfenadine being created by the use of fexofenadine has not been ruled out.
Cetirizine is another non-sedating antihistamine. However, in comparison to loratadine, cetirizine has been reported to have a higher incidence of adverse drug reactions (ADRs), especially central nervous system ADRs1. Some studies have also indicated that cetirizine has a higher incidence of somnolence than loratadine.
Loratadine is disclosed in U.S. Pat. No. 4,282,233 as a non-sedating antihistamine useful as an anti-allergy agent in, for example, the treatment of seasonal allergic rhinitis symptoms such as sneezing and itching. Loratadine has a maximum over the counter (OTC) dose of 10 mg per day. It is generally administered once a day at the maximum dose for a number of reasons including perceived efficacy and patient compliance. However, there are adverse effects that can occur at peak concentration and also with end-of-dose diminution of effect.
There are also a number of decongestant agents available. Phenylephrine has in the past been used as a decongestant agent. However, its use has now been surpassed by the next generation of decongestant products including pseudoephedrine. Pseudoephedrine tends to act with a higher efficacy and has a slightly longer half-life than previous generation products such as phenylephrine, providing an increase in the efficiency for relieving symptoms.
Combination antihistamine and decongestant products are available as a result of a demand for combination products that meet the problems associated with multiple product ingestion. Combinations of loratadine and new generation decongestants such as pseudoephedrine have been disclosed with a view to administering the combination once or twice a day. Disclosure of such combinations has been made in WO 98/18470 to Schering Corporation for example.
Combinations of the older style decongestant drugs, such as phenylephrine, and sedating antihistamines are available in liquid preparations. The use of such products has however been superseded by use of combinations using the newer style decongestant drugs, such as pseudoephedrine, for the reasons mentioned above.
There are several solid dose products currently available which combine the newer style drugs, such as pseudoephedrine, together with non-sedating antihistamine. Examples of those available in Australasia are given in Table 1 below.
TABLE 1Current Combination Non-Sedating Antihistamine and Nasal DecongestantSolid Dose Form Products Available in AustralasiaNon-sedatingProductDecongestantAntihistamineDaily DoseClarinasePseudoephedrineLoratadine 5 mg1 tablet twice12 Hour240 mgdailyClarinasePseudoephedrineLoratadine 10 mg1 tablet daily24 Hour240 mgReliefDemazin Non-PseudoephedrineLoratadine 5 mg1 tablet twiceDrowsy240 mgdailyTelfastPseudoephedrineFexofenadine 60 mg1 tablet twiceDecongestant240 mgdailyZyrtecPseudoephedrineCetirizine 5 mg1 tablet twiceDecongestant240 mgdaily
However, products containing pseudoephedrine are now subject to abuse problems associated with illicit drug use in the community. The pseudoephedrine component of these medications can be converted to potent stimulants such as methamphetamine and methcathinone both of which are CNS stimulants with great potential for habituation and physical and/or psychic dependence. This has resulted in pharmacy hold-ups, stolen stock from warehouses and significant related crime. The resulting crime, and its effects on the outlets which supply these medications to the market, means that some outlets are choosing not to stock these products, or at least restrict their availability. This makes them less accessible to those with a genuine need for the medications. In the United States, for example, legislation restricts the threshold content of pseudoephedrine OTC (“over the counter”) products, for example, can contain no more than 3 g of pseudoephedrine (in terms of the base) packaged in packs of 1 or 2 dosage units per pack or as package size liquid preparations.
It would be beneficial to have an alternative medication capable of being available without a prescription which is effective in treating the symptoms of upper respiratory mucosal congestion and which mitigates at least some of the problems identified above.
Other objects of the invention may become apparent from the following description, which is given by way of example only.